Modulation of Dapagliflozin-Associated Genital Tract Infections by Saxagliptin—A Pooled Safety Analysis

• Published in: Diabetes (New York, N.Y.) Vol. 67; no. Supplement_1
• Main Authors: PRATO, STEFANO DEL, JOHNSSON, EVA K., GARCIA-SANCHEZ, RICARDO, MORGAN, CLAIRE, SARTIPY, PETER, KURLYANDSKAYA, RAISA, IQBAL, NAYYAR, MATHIEU, CHANTAL
• Format: Journal Article
• Language: English
• Published: 01-07-2018
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/db18-1171-P

Incidence of genital tract infections (GTIs), a common adverse event during SGLT2 inhibitor therapy, may be modified by concomitant DPP-4 inhibitor treatment. We evaluated GTI incidence across randomized trials of dapagliflozin (DAPA) ± saxagliptin (SAXA) as add-on to metformin (MET). Safety data were pooled from seven randomized phase 3 trials; patients with type 2 diabetes (N=3134) receiving DAPA 5/10 mg, SAXA 5 mg or DAPA 5/10 mg + SAXA 5 mg as add-on to MET for 24-52 weeks were included. Data from patients with 52 weeks of follow-up across five of the studies were pooled separately (long-term [LT]-study pool; N=1719). In the 7-study pool, GTI incidence was lower with add-on DAPA 10 mg + SAXA 5 mg to MET vs. add-on of DAPA 10 mg alone (3.6% vs. 6.6%); the most common events in both groups were vulvovaginal mycotic infections (DAPA + SAXA, 1.5%; DAPA, 2.0%) and balanoposthitis (DAPA + SAXA, 0.9%; DAPA, 1.8%) (Table). This finding was confirmed in the individual studies with the exception of one study comparing GTI incidence with low-dose DAPA 5 mg + SAXA 5 mg (3.1%) vs. DAPA 5 mg (1.4%). With LT treatment, GTI incidence decreased over time with DAPA 10 mg + SAXA 5 mg and DAPA 10 mg (month 6, 3.1% and 5.3%; month 12, 0.9% and 2.1%).
In conclusion, add-on of DAPA 10 mg + SAXA 5 mg to MET led to lower GTI incidence than with DAPA 10 mg alone; this effect was maintained after 12 months of treatment.